• BIRC5-206
• CD40
• epithelial–mesenchymal transition
• miR-145-5p
• nasopharyngeal carcinoma

• expression profiles
• nasopharyngeal carcinoma
• prediction model
• regulatory mechanisms

• CDKN2A
• DNA methylation
• Epigenetics
• H3K27me3
• Histone
• Meningioma
• Methylation group
• Prognostic
• Recurrence

• ionizing radiation
• miRNA-149-5p
• microRNAs
• oncogenic factor
• tumor immunity
• tumor-suppressive factor

Nasopharyngeal carcinoma (NPC) arises from the epithelial cells located in the nasopharynx and has a distinct geographic distribution. Chronic Epstein-Barr virus (EBV) infection, as its most common causative agents, can be detected in 100% of NPC types. In-depth studies of the cellular and molecular events leading to immunosuppression in NPC have revealed new therapeutic targets and diverse combinations that promise to benefit patients with highly refractory, advanced and metastatic NPC. This paper reviews the mechanisms by which NPC cells to circumvent immune surveillance and approaches being attempted to restore immunity. We integrate existing insights into anti-NPC immunity and molecular signaling pathways as well as targeting therapies in anticipation of broader applicability and effectiveness in advanced metastatic NPC.

• LncRNA
• Macrophages
• Nanotoxicology
• Occupational health
• Zinc/copper (Zn/cu) metal fume exposure

• RWTH Aachen University (3131)

Long noncoding RNAs (lncRNAs) represent an important group of endogenous RNAs with limit protein-encoding capability, with a length of more than 200 nucleotides. Emerging evidence have demonstrated that lncRNAs are greatly involved in multiple cancers by playing critical roles in tumor initiation and progression. Long intergenic non-protein coding RNA 460 (LINC00460), a novel cancer-related lncRNA, exhibits abnormal expression and oncogenic function in multiple cancers, and positively correlates with poor clinical characteristics of cancer patients. LINC00460 has also been shown to be a promising biomarker for diagnosis as well as prognostic evaluation in cancer patients. In this review, we briefly summarized recent knowledge on the expression, functional roles, molecular mechanisms, and diagnostic and prognostic values of LINC00460 in human malignancies.

• Functional role
• Human cancer
• LINC00460
• Long noncoding RNA
• Molecular mechanism
• Oncogenic function

To study the feasibility of intensity modulated radiation therapy (IMRT) for stage N₀ nasopharyngeal carcinoma (NPC) and its parotid gland (PG) function preservation from physical and dosimetric aspects.

All the clinical data of 77 patients with pathologically confirmed T_1-4N₀M₀ NPC who received radiotherapy between July 2017 and October 2019 in the Radiotherapy Center of Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University were analyzed retrospectively. Three-dimensional conformal radiotherapy (3D-CRT) and IMRT were used in 35 and 42 cases, respectively. The treatment efficiency and the dosimetry differences of the PG in the intensity modulation plan were compared between groups. Quantitative monitoring of 99mTc radionuclide imaging of PG was performed before, at the end of, and 3, 6, and 12 months after radiotherapy. The degree of PG function injury and xerostomia was compared between groups at the end of radiotherapy and 12 months later.

Higher minimal, maximal, and average irradiation doses of PG were determined in 3D-CRT-treated patients compared with IMRT-treated cases (P < 0.05). Compared with before radiotherapy, the PG uptake index (UI) and excretion index (EI) of both cohorts of patients decreased to varying degrees at the end of radiotherapy, with PG function injury and xerostomia symptoms observed in all cases but with no obvious difference between groups (P > 0.05). To a certain extent, the PG function recovered and the xerostomia symptoms relieved in both groups 12 months after radiotherapy, with better improvements in IMRT group versus 3D-CRT group.

IMRT has similar short-term efficacy to 3D-CRT in treating patients with stage N₀ NPC, but it can effectively reduce the dose of PG radiotherapy and protect the PG function on the premise of ensuring sufficient tumor coverage and dose, showing certain dosimetry advantages.

The fatty acid metabolism (FAM) is known to impact tumorigenesis, tumor progression and treatment resistance via enhancing lipid synthesis, storage and catabolism. However, the role of FAM in head and neck squamous cell carcinoma (HNSCC) has remained elusive. In the present study, we obtained a total of 69 differentially expressed FAM-related genes between 502 HNSCC samples and 44 normal samples from The Cancer Genome Atlas (TCGA) database. The HNSCC samples were divided into 2 clusters according to 69 differentially expressed genes (DEGs) via cluster analysis. Then DEGs in the two clusters were found, and 137 prognostic DEGs were identified by univariate analysis. Subsequently, combined with the clinical information of 546 HNSCC patients from TCGA database, a 12-gene prognostic risk model was established (FEPHX3, SPINK7, FCRLA, MASP1, ZNF541, CD5, BEST2 and ZAP70 were down-regulation, ADPRHL1, DYNC1I1, KCNG1 and LINC00460 were up-regulation) using multivariate Cox regression and LASSO regression analysis. The risk scores of 546 HNSCC samples were calculated. According to the median risk score, 546 HNSCC patients were divided into the high- and low-risk (high- and low score) groups. The Kaplan-Meier survival analysis showed that the survival time of HNSCC patients was significantly shorter in the high-risk group than that in the low-risk group (p < 0.001). The same conclusion was obtained in the Gene Expression Omnibus (GEO) dataset. After that, the multivariate Cox regression analysis indicated that the risk score was an independent factor for patients with HNSCC in the TCGA cohort. In addition, single-sample gene set enrichment analysis (ssGSEA) indicated that the level of infiltrating immune cells was relatively low in the high-risk group compared with the low-risk group. In summary, FAM-related gene expression-based risk signature could predict the prognosis of HNSCC independently.

• Cancer therapy
• Prognosis
• Stanniocalcin 2
• Stress Response
• Tumorigenesis
• Tumour progression

• Efferocytosis
• apoptotic cell
• eat-me
• miRNA
• microRNA
• phagocytosis.

To clarify the effect of LINC00460 on mediating the proliferative ability of vascular endothelial cells (ECs) by targeting microRNA-24-3p (miRNA-24-3p), thus influencing the progression of atherosclerotic diseases.

Relative levels of LINC00460 and miRNA-24-3p in ECs induced with different doses of ox-LDL (oxidized low density lipoprotein) for different time points were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Influences of LINC00460 and miRNA-24-3p on the viability of ECs were assessed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assay. Through dual-luciferase reporter gene assay, the binding between LINC00460 and miRNA-24-3p was evaluated. At last, rescue experiments were performed to identify the function of the LINC00460/miRNA-24-3p axis in regulating the proliferative ability of ECs.

LINC00460 was upregulated after ox-LDL treatment in a dose- and time-dependent manner. Viability of ECs gradually increased with the prolongation of ox-LDL treatment and the treatment of increased dose. The overexpression of LINC00460 enhanced the viability and EdU-positive rate in ECs treated with ox-LDL. miRNA-24-3p was the direct target of LINC00460, which was negatively regulated by LINC00460. miRNA-24-3p was downregulated with the prolongation of ox-LDL treatment. The overexpression of miRNA-24-3p could reverse the effect of LINC00460 on regulating the proliferative ability of ECs.

LINC00460 regulates the proliferative ability of ECs and thus the occurrence and development of coronary atherosclerotic diseases by targeting miRNA-24-3p.

• Exosome
• Nasopharyngeal carcinoma
• Progression
• TP73-AS1
• miR-342-3p

• LINC00460
• cancer
• long non-coding RNA
• mechanism
• oncogene

• Biomarkers, Tumor/genetics
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• Neoplasms/genetics
• Neoplasms/pathology
• RNA, Long Noncoding/genetics
• Up-Regulation

• National Natural Science Foundation of China
• Natural Science Foundation of Shandong Province

• EMT
• LINC00839
• invasion
• miR-454-3p
• nasopharyngeal carcinoma

• Breast cancer
• SLC1A5
• circSEPT9
• miR-149-5p

• Amino Acid Transport System ASC/antagonists & inhibitors
• Amino Acid Transport System ASC/genetics
• Amino Acid Transport System ASC/metabolism
• Animals
• Apoptosis/genetics
• Base Sequence
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Cell Line, Tumor
• Cell Proliferation/genetics
• Dipeptides/pharmacology
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Gene Silencing/drug effects
• Glutamine/metabolism
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Minor Histocompatibility Antigens/genetics
• Minor Histocompatibility Antigens/metabolism
• Protein Binding/drug effects
• RNA, Circular/genetics
• RNA, Circular/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Mice

• FOXD1
• LINC00641
• carcinome du nasopharynx
• nasopharyngeal carcinoma

Calcific aortic valve disease (CAVD) is the most common structural heart disease, and the morbidity is increased with elderly population. Several microRNAs (miRNAs) have been identified to play crucial roles in CAVD, and numerous miRNAs are still waiting to be explored. In this study, the miRNA expression signature in CAVD was analyzed unbiasedly by miRNA-sequencing, and we found that, compared with the normal control valves, 152 miRNAs were upregulated and 186 miRNAs were downregulated in calcified aortic valves. The functions of these differentially expressed miRNAs were associated with cell differentiation, apoptosis, adhesion and immune response processes. Among downregulated miRNAs, the expression level of miR-139-5p was negatively correlated with the osteogenic gene RUNX2, and miR-139-5p was also downregulated during the osteogenic differentiation of primary human aortic valve interstitial cells (VICs). Subsequent functional studies revealed that miR-139-5p overexpression inhibited the osteogenic differentiation of VICs by negatively modulating the expression of pro-osteogenic gene FZD4 and CTNNB1. In conclusion, these results suggest that miR-139-5p plays an important role in osteogenic differentiation of VICs via the Wnt/β-Catenin pathway, which may further provide a new therapeutic target for CAVD.

• Wnt/b-catenin
• aortic valve interstitial cells
• calcific aortic valve disease
• miR-139-5p
• osteogenesis

• genome instability-related lncRNAs (GInLncRNAs)
• genomic instability
• lncRNA
• prognostic risk model
• renal cell carcinoma

• MiR-149-5p
• digestive system
• human cancers
• reproductive system
• respiratory system

• Cancer
• Long intergenic non-protein coding RNA 460
• Long non-coding RNA

• IL-6
• IL6-AS1
• chronic obstructive pulmonary disease
• early B-cell factor 1
• hsa-miR-149-5p
• inflammation
• long noncoding RNA

• Antagomirs/metabolism
• Cytokines/metabolism
• Cytoplasm/metabolism
• Fibroblasts/cytology
• Fibroblasts/metabolism
• Histones/metabolism
• Humans
• Interleukin-6/chemistry
• Interleukin-6/genetics
• Interleukin-6/metabolism
• Methylation
• MicroRNAs/antagonists & inhibitors
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Promoter Regions, Genetic
• Protein Binding
• Pulmonary Disease, Chronic Obstructive/genetics
• Pulmonary Disease, Chronic Obstructive/pathology
• RNA Interference
• RNA, Long Noncoding/antagonists & inhibitors
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Small Interfering/metabolism
• Trans-Activators/chemistry
• Trans-Activators/metabolism

• National Natural Science Foundation of China
• National Key Research and Development Program

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. Long noncoding RNAs were proved to be associated with the development and progression in HNSCC. However, the mechanism of LINC00460 in HNSCC needs to be further investigated. The study used quantitative real-time polymerase chain reaction assay to detect the expression of LINC00460 in cancer tissues and cell lines. Gain and loss of function experiments were conducted to analyze the effects of LINC00460 and miR-4443 on cell proliferation, invasion, and apoptosis of HNSCC cells in vitro. The interactions among miR-4443 and LINC00460 were detected by dual-luciferase reporter assay. Here, the study showed that LINC00460 was highly expressed in HNSCC tissues and cell lines. Functionally, knockdown of LINC00460 inhibited HNSCC cell proliferation and migration in vitro. Besides, LINC00460 promoted cell progression by sponging miR-4443, and miR-4443 inhibitor could reverse the effects of si-LINC00460 on cell proliferation and migration. In summary, LINC00460 could potentially promote cell progression and epithelial mesenchymal transition by sponging miR-4443 in HNSCC. LINC00460 could be used as a potential therapeutic target for HNSCCs.

• LINC00460
• head and neck squamous cell carcinoma
• long noncoding RNA
• miR-4443

• HNSCC
• TCGA
• biomarkers
• head and neck
• lincRNAs
• lncRNA
• non-coding RNA

• clear cell renal cell carcinoma (ccRCC)
• genomic instability (GI)
• long non-coding RNA (IncRNA)
• prognosis predicting
• risk signature
• somatic mutation profile
• therapeutic scheme deciding

• Biological functions
• Clinical applications
• Long non-coding RNAs (lncRNAs)
• Nasopharyngeal carcinoma (NPC)

• Biomarkers
• Head and neck squamous cell carcinoma
• Long non-coding RNAs
• Oral squamous cell carcinoma
• Prognosis
• Therapeutic targets

• KCNQ1 opposite strand/antisense transcript 1
• microRNA‑454
• ubiquitin specific peptidase 47
• nasopharyngeal carcinoma
• cisplatin resistance

• Blotting, Western
• Cell Line
• Cisplatin/pharmacology
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• Nasopharyngeal Carcinoma/genetics
• Nasopharyngeal Carcinoma/metabolism
• Potassium Channels, Voltage-Gated/genetics
• Potassium Channels, Voltage-Gated/metabolism
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Ubiquitin Thiolesterase/genetics
• Ubiquitin Thiolesterase/metabolism
• Ubiquitin-Specific Proteases/genetics
• Ubiquitin-Specific Proteases/metabolism

M2 macrophages can promote liver cancer metastasis by promoting tumour angiogenesis; however, the mechanism underlying macrophage polarization has not been completely revealed. In this study, we mainly explored the mechanism underlying long non‐coding RNA‐CRNDE (lncRNA‐CRNDE) in regulating M2 macrophage polarization and promoting liver cancer angiogenesis. The expression of CRNDE was up‐regulated or down‐regulated in THP‐1 cells (CRNDE^‐/‐‐THP‐1 cells and pcDNA3.1‐CRNDE‐THP‐1). THP‐1 cells were co‐cultured with liver cancer cell line H22, and M2 polarization was induced in THP‐1 by IL‐4/13 to simulate tumour‐induced macrophage polarization. As a result, after CRNDE overexpression, THP‐1 cell viability was up‐regulated, the expression of M2 membrane marker CD163 was up‐regulated, and the proportion of F4/80 + CD163+ cells was also up‐regulated. ELISA assay showed that the expression of M2 markers (including TGF‐β1 and IL‐10) and chemokines (including CCl22 and CCL22) was up‐regulated, and the expression of key signals (including STAT6, JAK‐1, p‐AKT1, and Arg‐1) was also up‐regulated, which were significantly different compared with the control group (Con). In addition, the intervention effect of CRNDE on THP‐1 was consistent between co‐culture with H22 cells and IL‐4/13 induction assay. The induced M2 THP‐1 cells were co‐cultured with HUVEC. As a result, THP‐1 cells with CRNDE overexpression can promote the migration and angiogenesis of HUVEC cells in vitro and simultaneously up‐regulate the expression of Notch1, Dll4 and VEGFR2, indicating that THP‐1 M2 polarization induced by CRNDE could further promote angiogenesis. The H22 cell tumour‐bearing mouse model was constructed, followed by injection of CRNDE anti‐oligosense nucleotides and overexpression plasmids to interfere CRNDE expression in tumour‐bearing tissues. Consequently, down‐regulation of CRNDE could down‐regulate tumour volume, simultaneously down‐regulate the expression of CD163 and CD31 in tissues, decrease the expression of key proteins (including JAK‐1, STAT‐6, p‐STAT6 and p‐AKT1), and down‐regulate the expression of key angiogenesis‐related proteins (including VEGF, Notch1, Dll4 and VEGFR2). In this study, we found that CENDE could indirectly regulate tumour angiogenesis by promoting M2 polarization of macrophages, which is also one of the mechanisms of microenvironmental immune regulation in liver cancer.

• M2 polarization
• long non-coding RNA-CRNDE
• macrophages
• microenvironment
• tumour blood vessels

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies. There is a growing body of evidence showing that long non‐coding RNAs (lncRNAs) play critical roles in ESCC oncogenesis. The present study aimed to explore the role of LOC101928477, a newly discovered lncRNA, in the development and metastasis of ESCC.

In this study, real‐time PCR, western blotting, cell counting kit‐8 (CCK‐8), flow cytometry, colony formation, wound healing, transwell migration/invasion assay, immunofluorescence, and immunohistochemistry were used. We also applied an in situ xenograft mouse model and a lung metastasis mouse model to verify our findings.

We determined that LOC101928477 expression was inhibited in ESCC tissue and ESCC cell lines when compared with controls. Moreover, forced expression of LOC101928477 effectively inhibited ESCC cell proliferation, colony formation, migration, and invasion via suppression of epithelial‐mesenchymal transition (EMT). Furthermore, LOC101928477 overexpression inhibited in situ tumor growth and lung metastasis in a mouse model.

Together, our results suggested that LOC101928477 could be a novel suppressor gene involved in ESCC progression.

• LOC101928477
• epithelial-mesenchymal transition
• esophageal squamous cell carcinoma

• AFAP1-AS1
• Nasopharyngeal carcinoma
• SP1
• miR-497-5p

• CELF1 Protein/metabolism
• Cell Line, Tumor
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• MicroRNAs/metabolism
• Microfilament Proteins/physiology
• Molecular Targeted Therapy
• Nasopharyngeal Carcinoma/genetics
• Nasopharyngeal Carcinoma/pathology
• Nasopharyngeal Neoplasms/genetics
• Nasopharyngeal Neoplasms/pathology
• Neoplasm Invasiveness/genetics
• RNA, Long Noncoding/physiology
• Signal Transduction/genetics
• Signal Transduction/physiology
• Sp1 Transcription Factor/physiology

• LINC01433
• Migration
• Nasopharyngeal carcinoma
• Proliferation
• miR-506-3p

There are an increasing number of studies indicating the important roles served by long non-coding RNAs (lncRNAs) in the development of different types of cancer. LINC00460 is a novel identified lncRNA that was found to be upregulated in colorectal cancer. However, the biological roles of LINC00460 in colorectal cancer have yet to be fully elucidated. This study was aimed to investigate the functions and molecular mechanisms of LINC00460 on colorectal cancer metastasis.

Expression of LINC00460 and biglycan (BGN) in colorectal cancer tissues and cell lines were quantified by real time PCR or western blotting assay. Cell migration and invasion assays were performed to determine the effect of LINC00460 on tumor metastasis in vitro. The binding interaction between microRNA-149-5p and LINC00460 was revealed by luciferase reporter assay.

In the present study, lncRNA LINC00460 was shown to be upregulated in colorectal cancer tissues, and overexpression of LINC00460 significantly promoted metastasis of colorectal cancer in vitro. Furthermore, miR-149-5p interacted with LINC00460, and they negatively regulated expression of each other. Transfection of miR-149-5p mimics partially counteracted the tumor metastasis-promoting effects induced by LINC00460 overexpression. Finally, overexpression of LINC00460 upregulated the expression levels of biglycan, a target gene of miR-149-5p, which has also been identified as an oncogenic driver in colorectal cancer.

Taken together, the present study demonstrated that LINC00460 promoted metastasis of CRC by sponging miR-149-5p and thereby affecting biglycan expression levels.

• LINC00460
• biglycan
• colorectal cancer
• metastasis
• miR-149-5p

Epstein–Barr virus-associated diseases are important global health concerns. As a group I carcinogen, EBV accounts for 1.5% of human malignances, including both epithelial- and lymphatic-originated tumors. Moreover, EBV plays an etiological and pathogenic role in a number of non-neoplastic diseases, and is even involved in multiple autoimmune diseases (SADs). In this review, we summarize and discuss some recent exciting discoveries in EBV research area, which including DNA methylation alterations, metabolic reprogramming, the changes of mitochondria and ubiquitin-proteasome system (UPS), oxidative stress and EBV lytic reactivation, variations in non-coding RNA (ncRNA), radiochemotherapy and immunotherapy. Understanding and learning from this advancement will further confirm the far-reaching and future value of therapeutic strategies in EBV-associated diseases.

• ATG5
• Circ-FOXM1
• cell development
• miR-149-5p
• non-small cell lung cancer

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, and its underlying mechanism remains unclear. Accumulating evidence has highlighted that long non-coding RNA (lncRNA) acts as competitive endogenous RNA (ceRNA) and plays an important role in the occurrence and development of LUAD. Here, we comprehensively analyzed and provided an overview of the lncRNAs, miRNAs, and mRNAs associated with LUAD from The Cancer Genome Atlas (TCGA) database. Then, differentially expressed lncRNAs (DElncRNA), miRNAs (DEmiRNA), and mRNAs (DEmRNA) were used to construct a lncRNA–miRNA–mRNA regulatory network according to interaction information from miRcode, TargetScan, miRTarBase, and miRDB. Finally, the RNAs of the network were analyzed for survival and submitted for Cox regression analysis to construct prognostic indicators. A total of 1123 DElncRNAs, 95 DEmiRNAs, and 2296 DEmRNAs were identified (|log₂FoldChange| (FC) > 2 and false discovery rate (FDR) or adjusted P value < 0.01). The ceRNA network was established based on this and included 102 lncRNAs, 19 miRNAs, and 33 mRNAs. The DEmRNAs in the ceRNA network were found to be enriched in various cancer-related biological processes and pathways. We detected 22 lncRNAs, 12 mRNAs, and 1 miRNA in the ceRNA network that were significantly associated with the overall survival of patients with LUAD (P < 0.05). We established three prognostic prediction models and calculated the area under the 1,3,5-year curve (AUC) values of lncRNA, mRNA, and miRNA, respectively. Among them, the prognostic index (PI) of lncRNA showed good predictive ability which was 0.737, 0.702 and 0.671 respectively, and eight lncRNAs can be used as candidate prognostic biomarkers for LUAD. In conclusion, our study provides a new perspective on the prognosis and diagnosis of LUAD on a genome-wide basis, and develops independent prognostic biomarkers for LUAD.

• Competing endogenous RNA network
• Cox regression
• Lung adenocarcinoma
• Overall survival
• Prognostic biomarker

Mounting evidence has demonstrated that circular RNAs (circRNAs) play indispensable roles in the progression of bladder cancer. Public database mining showed that hsa_circRNA_100146 (circRNA_100146) was highly expressed in bladder cancer. This study aimed to characterize the biological role of circRNA_100146 and clarify the underlying mechanism in bladder cancer.

We evaluated the relationship between circRNA_100146 expression and clinicopathological features. Furthermore, gain- and loss-of-function studies were conducted in bladder cancer cells via transfection with gene-carrying plasmids (over-expression) or specific short hairpin RNAs (knockdown). Moreover, computational algorithms and dual-luciferase reporter assays were performed to explore the possible mechanisms of action. Additionally, in vivo xenograft experiments were performed to further analyze the effect of circRNA_100146 on tumor growth.

Our data showed that circRNA_100146 expression was increased in bladder cancer tissues and cell lines, and that high expression of circRNA_100146 was correlated with poor patient prognosis. Upregulation of circRNA_100146 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, whereas knockdown of circRNA_100146 displayed opposite effects on bladder cancer cells. Notably, circRNA_100146 could combine with miR-149-5p and promote ring finger protein 2 (RNF2) expression, thereby facilitating the progression of bladder cancer. Furthermore, overexpression of RNF2 reversed the effects of circRNA_100146 knockdown on the biological behaviors of bladder cancer cells. The in vivo experiments revealed that downregulation of circRNA_100146 dramatically delayed tumor growth.

Our findings indicate that circRNA_100146 functions as a sponge of miR-149-5p in promoting bladder cancer progression by regulating RNF2 expression and that circRNA_100146 may serve as a novel biomarker in human bladder cancer.

• RNF2
• bladder cancer
• circRNA_100146
• invasion
• proliferation

• COX2
• lncRNA GAS5
• miR‑4465
• nasopharyngeal carcinoma

• Bladder carcinoma
• Forkhead Box K1
• LINC00460
• Progression
• miR-612

• Animals
• Cell Line, Transformed
• Cell Movement/genetics
• Cell Proliferation/genetics
• Cell Survival/genetics
• Disease Progression
• Female
• Forkhead Transcription Factors/metabolism
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Heterografts/growth & development
• Heterografts/metabolism
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/metabolism
• Middle Aged
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Up-Regulation
• Urinary Bladder Neoplasms/genetics
• Urinary Bladder Neoplasms/metabolism
• Urinary Bladder Neoplasms/pathology
• Mice

Long non-coding RNAs (lncRNAs) have been reported to serve a crucial role in the progression of nasopharyngeal carcinoma (NPC); however, the underlying molecular mechanisms of lncRNA KIF9-AS1 in the tumorigenesis of NPC remains poorly understood. Reverse transcription-quantitative PCR was used to analyze the expression levels of KIF9-AS1 and microRNA (miR)-16, and Cell Counting Kit-8, wound healing and Transwell assays were used to determine the cell viability, invasion and migration, respectively, of NPC cells. In addition, a dual-luciferase reporter assay was used to analyze the direct interaction between KIF9-AS1 and miR-16. NPC stage was classified according to the seventh edition of the AJCC staging system. The results revealed that KIF9-AS1 expression levels were upregulated in NPC tissues and cell lines. In addition, miR-16 was demonstrated to directly interact with KIF9-AS1 and inhibit KIF9-AS1 expression levels, whereas the miR-16 inhibitor rescued the effects of the KIF9-AS1-knockdown in NPC cells. Furthermore, the expression levels of KIF9-AS1 were upregulated, while those of miR-16 were downregulated in NPC tissues. Notably, the expression levels of KIF9-AS1 were observed to be significantly more upregulated in advanced tumors (III–IV vs. I–II) and patients with high KIF9-AS1 expression levels exhibited a worse prognosis. In conclusion, the findings of the present study suggested that KIF9-AS1 may promote the progression of NPC by targeting miR-16, thus KIF9-AS1 may be a novel molecular target for NPC therapy.

• KIF9-AS1
• competing endogenous
• miR-16
• nasopharyngeal carcinoma

• Competing endogenous RNA/ceRNA
• Head and neck squamous cell carcinoma/HNSCC
• LncRNA
• Prognosis
• TCGA

• CDK6
• lncRNA FAM133B-2
• miR-34a-5p
• nasopharyngeal carcinoma
• radio-resistance

Gastric cancer (GC) is a considerable health burden around the world. Circular RNA Nance-Horan syndrome-like 1 (circNHSL1) is reported to be highly expressed in GC. Nevertheless, the function and molecule mechanism of circNHSL1 are still unclear.

The expression levels of circNHSL1, microRNA-149-5p (miR-149-5p) and YWHAZ were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The subcellular fractionation identified the remarkable cytoplasmic localization of circNHSL1. Cell migration and invasion were measured by transwell assays. The levels of glutamine, glutamate and α-ketoglutarate (α-KG) were assessed by the corresponding kit. The protein levels of CD63, CD9, CD81, alanine, serine, cysteine-preferring transporter 2 (ASCT2), glutaminase 1 (GLS1), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) were detected by Western blot assay. The binding relationship between miR-149-5p and circNHSL1 or YWHAZ was predicted by starBase 3.0 and then verified by RNA pull-down and dual-luciferase reporter assays. Xenograft tumor model examined the biological role of circNHSL1 in vivo. Exosomes were examined by a transmission electron microscope and nanoparticle tracking analysis (NTA).

CircNHSL1 was highly expressed in GC cell-derived exosomes, GC tissues, and cells. Its knockdown impeded GC cell migration, invasion, and glutaminolysis. Mechanism analysis showed that circNHSL1 could affect YWHAZ expression by sponging miR-149-5p, thereby regulating GC progression. CircNHSL1 downregulation blocked GC tumor growth in vivo.

Our studies disclosed that circNHSL1 knockdown repressed migration, invasion, and glutaminolysis in vitro and inhibited tumor growth in vivo by miR-149-5p/YWHAZ axis in GC, implying an underlying circRNA-targeted therapy for GC treatment.

• YWHAZ
• circNHSL1
• gastric cancer
• miR-149-5p

Long-noncoding RNAs (lncRNAs) could exert a crucial effect on the development of human cancers, including CRC. However, the biological function and underlying mechanism of LINCRNA00460 in the development of CRC still need deeper exploration.

The expression of LINC00460 in CRC tissues and cell lines was assessed by qRT-PCR. Cell proliferation, migration, and invasion were measured by the respective cell counting Kit-8 (CCK-8), wound healing assay and transwell invasion assay. Cell apoptosis and caspase-3 activity were detected by flow cytometry and caspase-3 activity assay. The relationship between LINC00460 and miR-613 expression was explored by Dual-luciferase reporter assay. Protein expression was measured by Western blotting. In vivo tumour growth was evaluated using a xenograft model of nude mice.

LINC00460 was markedly up-regulated in CRC tissues and cell lines compared to their corresponding controls, which was closely correlated with clinical stage, TNM (T) classification, nodal (N) classification, metastasis (M) classification, liver metastasis and pathological differentiation, and survival rate of CRC patients. Functionally, LINC00460 knockdown decreased the proliferative, migrative and invasive abilities, and enhanced apoptosis rates and caspase-3 activity in HT29 and LOVO cells. Mechanistic studies indicated that miR-613 was targeted by LINC00460, and SphK1 was targeted and inversely regulated by miR-613 in HT29 and LOVO cells. In vivo studies, LINC00460 knockdown attenuated tumour growth. MiR-613 downregulation and SphK1 upregulation in the CRC tissues, and LINC00460 expression levels were inversely correlated with miR-613 expression and positively correlated with the SphK1 mRNA expression. Overall, LINC00460 modulated cell proliferation, migration, invasion and sphingosine kinase 1 (SphK1) expression in HT29 and LOVO cells, at least in most part, by regulating miR‐613.

LINC00460 functions as a competing endogenous RNA to regulate SphK1 expression by sponging miR‐613 in CRC and provides a valuable therapeutic strategy for CRC patients.

• SphK1
• colorectal cancer
• long noncoding RNA 00460
• miR‐613

• AKT serine/threonine kinase 2
• Cervical cancer
• High-mobility group protein AT hook 2
• Long non-coding RNA LINC00460
• MicroRNA-503-5p
• Short stature homeobox 2

• Animals
• Apoptosis/physiology
• Cell Cycle/physiology
• Cell Line, Tumor
• Cell Movement/physiology
• Cell Proliferation/physiology
• Cell Survival/physiology
• Databases, Genetic
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Survival Rate
• Uterine Cervical Neoplasms/genetics
• Uterine Cervical Neoplasms/metabolism
• Uterine Cervical Neoplasms/pathology
• Xenograft Model Antitumor Assays